Facile solvent-free generation of disulfide dianion and its use for preparation of symmetrical disulfides

Article abstract of DOI:10.1080/10426500701567269

A variety of symmetrical dialkyl disulfides were prepared from the reaction of alkyl halides, sodium hydroxide and elemental sulfur under solvent free conditions. The reaction proceeded very fast and produced the desired products in moderate to excellent isolated yields.

Full text of DOI:10.1080/10426500701567269

This article was downloaded by: [The University of Manchester Library]
On: 11 November 2014, At: 09:49
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Facile Solvent-Free Generation
of Disulfide Dianion and its Use
for Preparation of Symmetrical
Disulfides
Ali Reza Kiasat a , Babak Mokhtari a , Ali Savari a &
Foad Kazemi b
a Chemistry Department, College of Sciences ,
Shahid Chamran University , Ahwaz, Iran
b Department of Chemistry , Institute for Advanced
Studies in Basic Sciences (IASBS) , Gava Zang,
Zanjan, Iran
Published online: 20 Feb 2008.
To cite this article: Ali Reza Kiasat , Babak Mokhtari , Ali Savari & Foad Kazemi (2007)
Facile Solvent-Free Generation of Disulfide Dianion and its Use for Preparation of
Symmetrical Disulfides, Phosphorus, Sulfur, and Silicon and the Related Elements,
183:1, 178-182, DOI: 10.1080/10426500701567269
To link to this article: http://dx.doi.org/10.1080/10426500701567269
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the

Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 183:178–182, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701567269
Facile Solvent-Free Generation of Disulfide Dianion and
its Use for Preparation of Symmetrical Disulfides
Ali Reza Kiasat,1 Babak Mokhtari,1 Ali Savari,1
and Foad Kazemi2
1Chemistry Department, College of Sciences, Shahid Chamran
University, Ahwaz, Iran
2Department of Chemistry, Institute for Advanced Studies in Basic
Sciences (IASBS), Gava Zang, Zanjan, Iran
A variety of symmetrical dialkyl disulfides were prepared from the reaction of alkyl
halides, sodium hydroxide and elemental sulfur under solvent free conditions. The
reaction proceeded very fast and produced the desired products in moderate to
excellent isolated yields.
Keywords Alkyl halide; solvent free; sulfur; symmetrical dialkyl disulfides
INTRODUCTION
Dialkyl disulfides are an important class of compounds and have
received considerable attention in the literature. They are of inter-
est due to both: numerous biological properties1 and a rich syn-
thetic organic chemistry.2 The most common routes for the prepara-
tion of organic disulfides are the oxidation of thiols, which has been
carried out with many oxidizing agents,3 as well as various alky-
lation methods using sulfur nucleophiles including sulfur/NaOH in
refluxing methanol,4 sulfur/NaOH/phase transfer catalyst under mi-
crowave irradiation, sulfur/NaBH4,5 piperidinium tetrathiotungstate
7
or piperidinium tetrathiomolybdate,6 and Bunte salts. However, de-
spite the availability of many preparative procedures the restrictions
Received 27 April 2007; accepted 11 July 2007.
We are thankful to the Shahid Chamran University Research Council for partial
support of this work.
Address correspondence to Babak Mokhtari, Chemistry Department, College of Sci-
ences, Shahid Chamran University, Ahvaz 61357-43169, Iran. E-mail: bmokhtari@
scu.ac.ir
178

Solvent Free Synthesis of Symmetrical Disulfides
179
that accompany some of them, make new, mild, and practical methods
highly desirable.
RESULTS AND DISCUSSION
In continuation of our investigations on new methodologies for the syn-
thesis of organo-sulfur compounds,8 we recently published the first
solvent-free preparation of symmetrical organic disulfides under con-
ventional conditions using NaBH4/S8/wet neutral alumina.9 Here, we
report a revised procedure for a reproducible and scalable preparation
of dialkyl disulfides in high yields using S8/NaOH in the presence of
silica gel as solid support under solvent free conditions (Scheme 1). The
reaction procedure is very simple and includes the generation of the
disulfide anion under microwave irradiation and then the grinding of
the resulted dianion with an appropriate alkylating agent.
The scope and limitations of this transformation were determined
by the synthesis of several structurally diverse dialkyl disulfides from
the corresponding alkyl halides under our reaction conditions. The re-
action is generally fast, requiring from 5 to 10 min for completion in
most of the cases. Reduced rates were observed with secondary alkylat-
ing agents, such as cyclohexyl tosylate. Tertiary alkyl halides did not
afford the desired disulfides even after longer reaction times, or under
microwave irradiation. In addition the generation of the S2− dianion
can be performed under conventional heating (oil bath, 70–80◦C) in the
less than 20 min; at room temperature, the disulfide dianion was not
formed at all.
As previously reported,4 we suggest that this reaction proceeds via
the disulfide dianion (S22−), which is formed in the first step. In the
second step, the S2− dianion reacts with the respective alkyl halide to
produce the corresponding symmetrical disulfide.
In conclusion, the procedure described here is operationally simple
and allows a rapid and high-yielding conversion of alkyl halides and
alkyl tosylates to the corresponding symmetrical disulfides under very
SCHEME 1

180
A. R. Kiasat et al.
mild conditions. The method seems to be more convenient with respect
to other reports and can be used as a valid alternative to other methods,
so avoiding tedious purifications or the use of more toxic reagents.
EXPERIMENTAL
General
Products were characterized by comparison of their spectroscopic data
(1H and 13C NMR, IR) with those reported in the literature. All yields
refer to isolated products. The reactions were done in BUTANE mi-
crowave oven. The FT-IR spectra of neat samples between NaCl disks
were obtained on a BOMEM 450 instrument. The high-field NMR
1
spectra were obtained on a Brucker AC 400 instrument. H and 13C
chemical shifts are quoted relative to solvent resonance(s) as internal
standard.
General Procedure for Synthesis of Symmetrical Disulfides
The mixture of 3 mmol S8 and 3 mmol NaOH was exposed to microwave
irradiation in domestic microwave oven for 3 minutes at a power of 200
W. Subsequently 1 mmol of the appropriate alkyl halide or tosylate and
0.5 g of silica gel were added and the resulting mixture ground in a
mortar for the appropriate time (according to Table I). After completion
of the reaction (monitored by TLC), the pure product was extracted with
CH2Cl2. The solvent was removed under reduced pressure to afford the
product, in almost pure form, which was further purified by column
chromatography on silica gel (hexane/ethyl acetate 9:1).
Typical Procedure for the Large-Scale Synthesis
of o-Bromo-Benzyl Disulfide
A mixture of S8 (60 mmol) and NaOH (60 mmol) was exposed to mi-
crowave irradiation in a domestic microwave oven for 3 minutes at the
appropriate power of the microwave oven (200 W). Subsequently, 1-
bromo 2-chloromethyl benzene (20 mmol) and 0.5 g of silica gel were
added and the resulting mixture was ground in a mortar for the ap-
propriate time (according to Table I). After completion of the reaction
(monitored by TLC), the product was extracted with CH2Cl2. The sol-
vent was removed under reduced pressure to afford the disulfide in
almost pure form. It was further purified by column chromatography
on silica gel (hexane/ethyl acetate 9:1).

Solvent Free Synthesis of Symmetrical Disulfides
181
TABLE I Preparation of Symmetrical Disulfides Using S8/NaOH
M.p. ◦
(lit)
C
(min) Yield
(min) (%)a
RX
Producta
Chloromethyl-benzene
69–71(69–70)10
3
92
1-Bromo-2-chloromethyl-
benzene
86–88 (87–88)4
3
90
1-Chloro-4-chloromethyl-
benzene
60–62 (59–60)4
75–78 (76–80)10
3
5
94
87
1-Bromomethyl-4-methoxy-
benzene
1-Bromo-butane
1-Bromo-hexane
Liquid11
Oil11
Oil11
30
10
10
68
72
90
Toluene-4-sulfonic acid octyl
ester
Bromo-acetonitrile
Oil9
Oil9
5
5
65
67
65
3-Bromo-propionitrile
Toluene-4-sulfonic acid
cyclohexyl ester
127–130
15
(125–130)12
Chlorotriphenylmethane
No Reaction
—
15
—
aAll products were identified by their IR and NMR spectral data and comparison of
their m.p. with published data; and bisolated pure product.
REFERENCES
[1] (a) W. W. Wong, S. MacDonald, R. F. Langler, and L. Z. Penn, Anticancer Res., 20,
1367 (2000); (b) J. A. MacDonald and R. F. Langler, Biochem. Biophys. Res. Commun.,
273, 421 (2000); (c) J. A. MacDonald, M. E. Marchand, and R. F. Langler, Blood
Coagulation and Fibrinolysis, 15, 447 (2004).
[2] S. Oae, Organic Sulfur Chemistry: Structure and Mechanism ( CRC, Boca Raton,
1991).
[3] G. Capozzi and G. Modena, The Chemistry of Thiol Group (Wiley, New York, 1974),
p. 785.
[4] J.-X. Wang, L. Gao, and D. Huang, Synth. Commun., 32, 963 (2002).
[5] B. P. Bandgar, L. S. Uppalla, and V. S. Sadavarte, Tetrahedron Lett., 42, 6741 (2001).
[6] P. Dhar and S. Chandrasekaran, J. Org. Chem., 54, 2998 (1989).
[7] H. Distler, Angew. Chem. Int. Ed. Engl., 6, 544 (1967).
[8] (a) A. R. Kiasat, F. Kazemi, and M. Fallah, Phosphorus, Sulfur, and Silicon, 179,
1841 (2004); (b) F. Kazemi, A. R. Kiasat, and S. Sayyahi, Phosphorus, Sulfur, and

182
A. R. Kiasat et al.
Silicon, 179, 1813 (2004); (c) F. Kazemi, A. R. Kiasat, and S. Ebrahimi, J. Chem.
Res. (S), 176 (2002).
[9] A. R. Kiasat, B. Mokhtari, F. Kazemi, S. Yousefi, and M. Javaherian, J. Sulfur Chem.,
28, 171 (2007).
[10] J. A. Gladysz, V. K. Wong, and B. S. Jick, Tetrahedron, 35, 2329 (1979).
[11] A. K. Misra and G. Agnihotri, Synth. Commun., 34, 1079 (2004).
[12] P. Zhong and M.-P. Guo, Synth. Commun., 31, 1825 (2001).
[13] A. Shaabani, F. Teimouri, and D. G. Lee, Synth. Commun., 33, 1057 (2003).